Discovery of Novel Quinazolinone-2-carbohydrazide Derivatives as Effective Succinate Dehydrogenase Inhibitors and Biosafety Assessment on Rice and Zebrafish
Journal of Agricultural and Food Chemistry,
Год журнала:
2025,
Номер
73(9), С. 5054 - 5066
Опубликована: Фев. 18, 2025
To
develop
potent
and
safe
antifungal
agents
in
agriculture,
a
total
of
48
novel
quinazolinone-2-carbohydrazide
derivatives
were
designed
synthesized
based
on
the
pharmacophore
hybridization
method.
The
bioassay
results
demonstrated
that
many
compounds
exhibited
powerful
broad-spectrum
inhibition
activities
vitro
against
tested
fungi.
For
instance,
E23
F23
possessed
EC50
(half-maximal
effective
concentration)
values
0.41
0.47
μg/mL
Rhizoctonia
solani,
comparable
to
commercial
fungicide
Boscalid
(EC50
=
0.49
μg/mL).
Additionally,
compound
also
pronounced
effects
Verticillium
dahliae,
Alternaria
Colletotrichum
gloeosporioides
with
0.27,
1.15,
0.27
μg/mL,
respectively.
In
vivo
assays
rice
plants
revealed
this
at
200
nearly
equipotent
curative
protective
R.
as
compared
positive
controls
Carbendazim.
Moreover,
had
an
obvious
activity
fungal
succinate
dehydrogenase
(SDH)
from
solani
half-maximal
concentration
(IC50)
11.76
μM,
interactions
between
SDH
enzyme
further
confirmed
by
molecular
docking
studies.
Furthermore,
presence
triggered
morphological
changes
mycelia
increased
conductivity
permeability
cell
membranes.
Interestingly,
built
three-dimensional
quantitative
structure-activity
relationship
(3D-QSAR)
models
showed
electrostatic
effect
played
more
important
role
maintaining
anti-R.
target
than
other
effects.
Finally,
biosafety
assessment
its
safety
toward
zebrafish.
Язык: Английский
Discovery of New Benzohydrazide Derivatives Containing 4-Aminoquinazoline as Effective Agricultural Fungicides, the Related Mechanistic Study, and Safety Assessment
Journal of Agricultural and Food Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 23, 2025
A
total
of
38
new
benzohydrazide
derivatives
bearing
the
4-aminoquinazoline
moiety
were
designed
and
synthesized
based
on
active
subunit
combination
approach
tested
in
detail
for
their
inhibition
activities
against
eight
agricultural
phytopathogenic
fungi.
The
bioassay
results
indicated
that
many
compounds
exhibited
extraordinary
fungicidal
vitro
For
example,
A5,
A6,
A11,
A17
had
EC50
(half-maximal
effective
concentration)
values
0.66,
0.71,
0.40,
0.42
μg/mL
Colletotrichum
gloeosporioides,
respectively,
comparable
to
boscalid
(0.36
μg/mL)
much
superior
carbendazim
(6.96
μg/mL).
Of
particular
importance
was
compound
A6
with
a
3,4-difluorophenyl
group
found
possess
good
broad-spectrum
antifungal
effects,
ranging
from
0.63
3.82
In
vivo
assays
also
revealed
curative
protective
efficacies
72.6%
78.9%
at
200
Rhizoctonia
solani-caused
rice
sheath
blight,
higher
than
those
(70.7
65.2%,
respectively).
Moreover,
mechanism-of-action
studies
disrupted
cell
membrane
integrity
R.
solani,
as
proved
by
relative
conductivity
measurements,
leakage
cellular
contents,
fluorescence
microscopy,
scanning
electron
microscopy
observations.
Significantly,
this
an
succinate
dehydrogenase
(SDH)
solani
inhibitory
concentration/IC50
=
11.02
μM),
slightly
weaker
SDH
inhibitor
(5.17
μM).
Further
molecular
docking
analysis
could
form
strong
interactions
key
residues
enzyme
via
hydrogen
bond,
electrostatic,
π-cation
interactions,
holding
promise
acting
fungicide
leads
targeting
SDH.
Finally,
safety
assessments
safe
honeybees.
Язык: Английский
Design, synthesis, crystal structure, fungicidal activity, and mechanism of action of novel thiazole-based hydrazide derivatives containing the 4-aminoquinazoline moiety
Bioorganic Chemistry,
Год журнала:
2025,
Номер
156, С. 108237 - 108237
Опубликована: Фев. 2, 2025
Язык: Английский
Novel Naphthyl and Phenyl Maleimide Derivatives: Molecular Design, Systematic Optimization, Antifungal Evaluation, and Action Mechanism
Journal of Agricultural and Food Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 29, 2025
A
systematic
optimization
strategy,
as
an
effective
screening
approach
for
new
antifungal
compounds,
was
implemented
to
rationally
construct
novel
naphthyl
and
phenyl
maleimide
derivatives.
The
structures
of
molecules
A32
B6
were
further
confirmed
by
single-crystal
X-ray
diffraction.
in
vitro
activity
evaluation
showed
that
the
target
compound
obtained
structure
exhibited
excellent
inhibition
(EC50
=
0.59
μg/mL)
against
Rhizoctonia
solani,
which
better
than
control
agent
dimethachlone
(1.21
μg/mL).
Further
vivo
experiments
on
rice
leaves
potted
plants
R.
solani
at
200
μg/mL
possessed
outstanding
protective
efficiency
compared
dimethachlone.
mycelium
morphology
observation
SEM
indicated
(25
severely
damaged
surface
mycelium,
accordance
with
increased
result
cell
membrane
permeability
assay.
MD
simulations
molecular
docking
analysis
revealed
compounds
A1
have
a
similar
binding
mode
active
pocket
plasma
H+-ATPases
(PMA1)
reference
fungicide
fluoroimide.
In
particular,
there
more
hydrogen
bonds
protein
complex
complexes
This
research
constructing
derivatives
strategy
provides
practical
way
find
leads,
thereby
developing
fungicides.
Язык: Английский
Resistance Risk Assessment of Propiconazole in Rhizoctonia solani and its Synergistic Antifungal Mechanism with Kresoxim-methyl
Journal of Agricultural and Food Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 19, 2025
The
resistance
risk
and
mechanisms
of
propiconazole
in
Rhizoctonia
solani
remain
unclear.
In
this
study,
the
sensitivity
159
R.
isolates
to
was
determined,
EC50
value
0.2286
μg/mL.
Nineteen
propiconazole-resistant
mutants
were
obtained
through
fungicide
adaptation,
compound
fitness
indexes
these
lower
than
those
their
parental
isolates.
Cross-resistance
analysis
revealed
that
there
no
cross-resistance
between
other
fungicides,
apart
from
prochloraz.
Although
point
mutations
occurred
RsCYP51
gene
or
its
promoter
regions,
expression
levels
efflux
transporter
genes
increased
substantially
mutants.
Furthermore,
a
1:1
synergistic
combination
kresoxim-methyl
(SCpk(1:1))
could
simultaneously
cause
more
severe
damage
both
cell
membrane
integrity
mitochondrial
function.
Field
trials
demonstrated
SCpk(1:1)
achieved
over
86%
control
efficacy
against
rice
sheath
blight
applied
at
120
g
a.i./ha.
Язык: Английский